In the area of PAH carcinogenesis we have quantified CYP1A1 RNA transcripts, and shown that the RNA transcripts, protein quantity and enzyme activity for CYP1A1 all correlate with formation of r7, t8, t9-trihydroxy-c-10-(N2-deoxyguanosyl)-7,8,9,10-tetrahydro-benzo[a]-pyrene (BPdG), the major DNA adduct of benzo(a)pyrene (BP). The carcinogenic PAH, BP, is thought to bind covalently to DNA through metabolism by Cytochrome P450 1A1 (CYP1A1) and CYP1B1, and other enzymes. Evaluation of RNA expression data, to understand the contribution of different metabolic enzymes to BPdG formation, is typically presented as fold-change observed upon BP exposure, leaving the actual number of RNA transcripts unknown. In this study we quantified RNA copies/ng cDNA (RNA cpn) for CYP1A1 and CYP1B1, as well as NAD(P)H:Quinone Oxidoreductase 1 (NQO1), which may reduce formation of BPdG adducts, using primary normal human mammary epithelial cell (NHMEC) strains, and the MCF-7 breast cancer cell line. In unexposed NHMECs, basal RNA cpn values were 56-836 for CYP1A1, 336-5587 for CYP1B1, and 5943-40112 for NQO1. In cells exposed to 4.0 micromolar BP for 12h, RNA cpn values were 251-13234 for CYP1A1, 4133-57077 for CYP1B1, and 4456-55887 for NQO1. There were 7.82 [0.2-15.8] (median [range]) BPdG adducts/108 nucleotides in the NHMECs (n=16), and 790 in the MCF-7s. In the NHMECs, BP-induced CYP1A1 RNA cpn was highly associated with BPdG (p=0.002), but CYP1B1 and NQO1 were not. Western blots of 4 NHMEC strains, chosen for different levels of BPdG adducts, showed a linear correlation between BPdG and CYP1A1, but not CYP1B1 or NQO1. Ethoxyresorufin-O-deethylase (EROD) activity, which measures CYP1A1 and CYP1B1 together, correlated with BPdG, but NQO1 activity did not. Despite more numerous levels of CYP1B1 and NQO1 RNA cpn in unexposed and BP-exposed NHMECs and MCF-7cells, BPdG formation was only correlated with induction of CYP1A1 RNA cpn. The higher level of BPdG in MCF-7 cells, compared to NHMECs, may have been due to a much increased induction of CYP1A1 and EROD. Overall, BPdG correlation was observed with CYP1A1 protein and CYP1A1/1B1 enzyme activity, but not with CYP1B1 or NQO1 protein, or NQO1 enzyme activity. In the area of Tamoxifen (TAM) carcinogenesis, the formation of TAM-DNA adducts in human endometrium is a controversial topic of interest, as TAM-exposed women are at risk for endometrial cancer. We have examined this question in multiple tissues of aging Erythrocebus patas (patas) monkeys given oral TAM dosing, as well as in human endometrial biopsy samples. In the patas monkeys and in humans, normal endometrium or endometrial tumor from individuals receiving TAM all had measurable TAM-DNA values, while no TAM-DNA adducts were detected in monkeys and in patients not receiving TAM therapy. The data show that TAM-DNA adducts are formed in endometrium of human patients, and that DNA damage may contribute to the risk of endometrial cancer. Because TAM is an estrogen antagonist in the breast but an estrogen agonist and carcinogen in the uterus, we hypothesized that comparison of gene expression patterns in cultured normal human breast and endometrial cells may elucidate TAM-induced mechanisms. Gene expression studies in TAM-exposed normal human mammary epithelial cells (NHMECs) showed TAM-induced up-regulation of interferon signaling and complement pathways. To contrast breast with endometrium, we examined TAM-exposed human endometrial stromal cells (HESC cells), and found the up-regulated genes to be primarily involved with biosynthesis of steroids and proliferation. In both breast and endometrial cells, microarray expression changes of the most highly altered genes were confirmed by quantitative RT-PCR. Pathway analysis showed that each cell type (breast and endometrium) induced different genes when both were exposed to the same dose of TAM for 48 hr. Immune-response pathways were predominantly induced in human breast, and steroidal and proliferative pathways were predominantly induced in human endometrium.